The Planning Grants for Engineering Research Centers competition was run as a pilot solicitation within the ERC program. Planning grants are not required as part of the full ERC competition, but intended to build capacity among teams to plan for convergent, center-scale engineering research.
Development of continuous membrane-enabled manufacturing of pharmaceuticals will open hitherto nonexistent opportunities for both conventional and reactive separations in the chemical, fine chemicals and petrochemical industries. Membrane technologies are compact, modular, easily scalable, highly energy efficient and are capable of extraordinary separations in a continuous fashion. Membrane reactors can achieve a synthesis level not achievable by conventional tubular reactors and are now well-established as a process intensification tool. To overcome many deficiencies of batch manufacturing, we propose an ERC for Continuous Membrane-Enabled Manufacturing of Pharmaceuticals (CMMP) using membrane technologies. The proposed ERC has three goals: (1) Develop, adapt and transition new membranes, novel membrane technologies and membrane reaction-separation concepts developed by the CMMP team and others into individual steps of continuous manufacturing of active pharmaceutical ingredients (APIs) in the molecular weight range of about 150-1000 Da; (2)Integrate the individual membrane-based steps into a multistep API production process and demonstrate the feasibility of a primarily membrane-based continuous process equipped with process analytical technology (PAT) to synthesize APIs economically with high efficiency, quality, and safety;(3) Develop an educational program and foster an environment that transforms education relevant to pharmaceutical production as well as influences fine chemicals manufacturing processes with the program-developed innovations.
In this Planning Grant, academic stakeholders from six universities will work with stakeholders from major pharmaceutical companies, contract manufacturing organizations, membrane manufacturers, and process system developers to identify key pharmaceutical systems with synthesis-cum-separation steps ready for introduction of new membrane technologies. During this grant, stakeholders will deliberate on potential membrane-based demonstration systems for multistep synthesis of select APIs. These systems will form the basis of the ERC pre-proposal. A stakeholder community will be formed to guide progress of CMMP and creation of a strong academic program to assist high school, undergraduate and graduate students learn the paradigm change when transitioning from batch production into continuous membrane-based API manufacturing. Membrane technologies have very limited footprint in pharmaceutical manufacturing due to perceived concerns regarding reduced solvent resistance and limited selectivities in organic solvent-based systems. New dense membranes are emerging with very high solvent resistance (HSR) and exquisite selectivities that can separate mixtures of smaller molecules and organic solvents via processes such as, organic solvent reverse osmosis, organic solvent nanofiltration and membrane pervaporation. Their further development will usher in a new era of membranes with extraordinary performance and understanding of how to design them. Microporous HSR membranes can be used for nondispersive solvent extraction, gas-liquid membrane contactors and reactors for hydrogenation, dehydrogenation, ozonation, membrane mixing, crystallization and adsorption. Dense, nanoporous membranes may be used in membrane reactors to achieve high selectivity and yield. Introduction of such membranes operating continuously into each step of the API synthesis train will radically transform pharmaceutical production introducing high efficiencies with compact/scalable membrane modules. This grant will allow stakeholders to identify membrane processes for API production that substantially enhance performances of reaction and separation steps. This grant will also guide an ERC pre-proposal in selecting API synthesis examples having a train of continuously operated membrane-based reaction and separation steps thereby demonstrating the capability of membrane devices to operate with high efficiency and reduced cost.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
